Among polyphenols, trans-resveratrol (tRES) and trans-polydatin (tPD) exert multiple
biological effects, particularly antioxidant and antiproliferative. In this work,
we have investigated the interaction of tPD with three cancer-related DNA sequences
able to form G-quadruplex (G4) structures, as well as with a model duplex, and compared
its behaviour with tRES. Interestingly, fluorescence analysis evidenced the ability
of tPD to bind all the studied DNA systems, similarly to tRES, with tRES displaying
a higher ability to discriminate G4 over duplex with respect to tPD. However, neither
tRES nor tPD produced significant conformational changes of the analyzed DNA upon
binding, as determined by CD-titration analysis. Computational analysis and biological
data confirmed the biophysical results: indeed, molecular docking evidenced the stronger
interaction of tRES with the promoter of c-myc oncogene, and immunoblotting assays
revealed a reduction of c-myc expression, more effective for tRES than tPD. Furthermore,
in vitro assays on melanoma cells proved that tPD was able to significantly reduce
telomerase activity, and inhibit cell proliferation, with tRES producing higher effects
than tPD.